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Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials Research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of Traditional Chinese Medicine Pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota Inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

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Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

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Acta Pharmaceutica Sinica B 2024年第1期14卷 273-291页

作者： Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park Department of Pharmacology Hanoi University of PharmacyHanoi 100000Viet Nam college of pharmacy Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Medical Biotechnology Yeungnam UniversityGyeongsan 38541Republic of Korea Research Institute of Cell Culture Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Precision Medicine School of MedicineSungkyunkwan UniversitySuwon 16419Republic of Korea

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese *** this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of ***-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese *** effects were also observed in lean *** addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced ***,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a *** findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关键词： Adiponectin Adipose-derived stromal cells Colitis Glycolytic induction HIF1a Immunomodulation Mesenchymal stromal cells Obesity

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A Network Pharmacology Study on Active Components and Targets of Citri Reticulatae Pericarpium for Treating Keloids

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Medicinal Plant 2024年第1期15卷 18-23,31页

作者： Chang REN Ru CHEN Lei SONG Kun GUO Liying QIU college of pharmacy Southwest Minzu UniversityChengdu 610041China

[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO *** Chinese medicine compound-target network was constructed by Cytoscape ***,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also ***,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the *** the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating *** genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling *** molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling *** present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.

关键词： Network pharmacology Keloids Citri Reticulatae Pericarpium

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A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2

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Chinese Chemical Letters 2024年第8期35卷 201-204页

作者： Yang Liu Yan Liu Kaiyin Yang Zhiruo Zhang Wenbo Zhang Bingyou Yang Hua Li Lixia Chen Wuya college of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Basic and Application Research of Beiyao Ministry of EducationHeilongjiang University of Chinese MedicineHarbin 150006China Institute of Structural Pharmacology&TCM Chemical Biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Hexokinase 2(HK2)is the rate-limiting enzyme in the first step of glycolysis,catalyzing glucose to glucose-6-phosphate,and overexpressed in most cancer ***2 also binds to voltage-dependent anion channel(VDAC)to stabilize the mitochondrial outer membrane,which inhibits cancer cell ***,HK2 has become a potential target for cancer *** targeting chimeras(PROTACs)are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted *** potent and specific PROTACs targeting dissimilar targets have been *** this study,an HK2 PROTAC,4H-5P-M,was developed and induced the degradation of HK2 relying on the ubiquitin-proteasome *** was found that 4H-5P-M as an effective HK2 degrader induced HK2 degradation in a dose-and time-dependent manner and suppressed the growth of SW480 cells.4H-5P-M selectively induced HK2 degradation at a lower concentration than other hexokinase ***,it could suppress glycolysis and accelerate the apoptosis of cancer ***,it provided a new insight into the development of anti-tumor drugs.

关键词： HK2 PROTACs Degrader Anti-tumor SW480

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The Influence of Depression on Different Age and Gender Groups in Bahawalpur

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Journal of Clinical and Nursing Research 2024年第7期8卷 196-207页

作者： Mehran Khan Muhammad Shahbaz Tooba Waris Shoaib Yaseen Iqra Afzal Emaan Khadim Sawera Usman Muhammad Ismail Shah Sulaiman Aslam Zafar Iqbal Bahawalpur college of pharmacy BMDC Complex63100PunjabPakistan

In Bahawalpur,a cross-sectional study assessed depression prevalence across age and gender groups,involving 442 participants from diverse socioeconomic backgrounds and *** the PHQ9 questionnaire,84%were found to meet depression *** findings revealed a higher incidence in females(88%)than males(79%),with the greatest disparity among young adults,particularly young women,due to factors like academic pressure and financial *** children had the lowest depression rates(68%),possibly due to better *** individuals exhibited more severe depression,likely related to aging and domestic *** study’s findings highlight a significant variation in depression severity across different demographic groups,with an overall higher incidence in *** research underscores the necessity for targeted mental health resources and interventions tailored to the specific needs of each demographic *** also points to the importance of addressing academic and socioeconomic stressors to mitigate depression,particularly among young *** the study provides valuable insights,it relies on self-reported data,which may introduce ***,future research should include clinical assessments to validate these findings and ensure a more accurate representation of depression within the community.

关键词： Influence Depression Different age Gender groups Bahawalpur

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UV,five wavelengths fusion and electrochemical fingerprints combined with antioxidant activity for quality control of antiviral mixture

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Asian Journal of Traditional Medicines 2024年第3期19卷 119-136,151页

作者： Kaining Zhou Zini Tang Guoxiang Sun Ping Guo Lili Lan college of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

Aiming to ensure the consistency of quality control of Traditional Chinese Medicines(TCMs),a combination method of high-performance liquid chromatography(HPLC),ultraviolet(UV),electrochemical(EC)was developed in this study to comprehensively evaluate the quality of Antiviral Mixture(AM),and Comprehensive Linear Quantification Fingerprint Method(CLQFM)was used to process the *** analysis of three active substances in TCM was conducted.A fivewavelength fusion fingerprint(FWFF)was developed,using second-order derivatives of UV spectral data to differentiate sample levels *** combination of HPLC and UV spectrophotometry,along with electrochemical fingerprinting(ECFP),successfully evaluated total active ***,a multidimensional profiling analytical system for TCM was developed.

关键词： TCM antiviral mixture five-wavelength fusion fingerprint(FWFF) Comprehensive Linear Quantification Fingerprint Method(CLQFM) quantization fingerprint antioxidant activity profilling

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Innovative hydrogel-based delivery systems for immunotherapy:A review of pre-clinical progress

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Nano Research 2024年第10期17卷 9031-9043页

作者： Narsimha Mamidi Michael Poellmann Kaila Javius-Jones KiChang Nam Seungpyo Hong Wisconsin Center for NanoBioSystems University of Wisconsin-MadisonMadisonWI 53705USA Pharmaceutical Sciences Division School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA Department of Medical Engineering College of MedicineDongguk UniversityGoyang 10326Republic of Korea Department of pharmacy Yonsei UniversityIncheon 21983Republic of Korea Lachman Institute for Pharmaceutical Development University of Wisconsin-MadisonMadisonWI 53705USA

Immunotherapy has markedly reinvented how we treat cancer,as shown by numerous Food and Drug Administration(FDA)drug approvals that have made significant clinical impact and ongoing clinical ***,undesirable side effects,such as autoimmunity and inflammation,and inconsistent clinical outcomes remain a major *** response rates across various immunotherapeutic reagents is imperative to enhance overall effectiveness and reduce adverse side *** address this challenge,interdisciplinary approaches have been explored by incorporating immunotherapies into hydrogels,enabling finecontrolled delivery to target *** review focuses on recent progress in the utilization of hydrogel-based delivery systems for cancer immunotherapy and their potential to further enhance treatment response ***,recent preclinical advances in hydrogels implemented with immune checkpoint inhibitors,combination therapies,and vaccines,along with selfassembled peptide hydrogels,are *** also discuss technological advances and drawbacks in this area and provide insights to ultimately realize the clinical application of hydrogels in cancer immunotherapy.

关键词： cancer immunotherapy drug delivery hydrogels immunotherapeutic agents immune modulation clinical outcomes

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Single-cell transcriptomics reveals T-cell heterogeneity and immunomodulatory role of CD4+T native cells in Candida albicans infection

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BIOCELL 2024年第9期48卷 1355-1368页

作者： KERAN JIA YANHAO ZHANG MENGYU JIANG MENGGE CUI JIA WANG JIAJIA ZHANG HUIHAI ZHAO MENGYAN LI HUA WANG QUANMING ZOU HAO ZENG National Engineering Research Center of Immunological Products Department of Microbiology and Biochemical PharmacyCollege of PharmacyArmy Medical UniversityChongqing400038China Department of Clinical Laboratory The 980th Hospital of PLA Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang050082China

Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi *** the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal ***:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western *** investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans ***:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell ***,CD4^(+)T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T *** addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+)T cell ***:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.

关键词： Candida albicans Single-cell transcriptomics Immune microenvironment Fungal infections Hub gene

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Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4001-4013页

作者： Ziqi Huang Kun Zhang Yurui Jiang Mengmeng Wang Mei Li Yuda Guo Ruolin Gao Ning Li Chenyang Wang Jia Chen Jiefu Wang Ning Liu Xiang Liu Shuangwei Liu Mingming Wei Cheng Yang Guang Yang The State Key Laboratory of Medicinal Chemical Biology College of Life SciencesCollege of PharmacyNankai UniversityTianjin 300071China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

Cancer stem cells(CSCs)play a pivotal role in tumor initiation,proliferation,metastasis,drug resistance,and ***,targeting CSCs has emerged as a promising avenue for cancer ***,3-phosphoglycerate dehydrogenase(PHGDH)has been identified as being intricately associated with the regulation of numerous cancer stem ***,reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are *** this study,the novel“molecular glue”LXH-3-71 was identified,and it robustly induced degradation of PHGDH,thereby modulating the stemness of colorectal cancer cells(CRCs)both in vitro and in ***,LXH-3-71 was observed to form a dynamic chimera,between PHGDH and the DDB1-CRL E3 *** insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH ***,compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase,facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

关键词： Molecular glue Targeted protein degradation PHGDH Cancer stem cells PROTACs

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Tb^(3+)-nucleic acid probe-based label-free and rapid detection of mercury pollution in food

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Food Science and Human Wellness 2024年第2期13卷 993-998页

作者： Xuhan Xia Chenxi Zhou Yulin Zhu Yi Dong Qiang He Mohammad Rizwan Khan Yuanlong Chi Rosa Busquets Ruijie Deng Yao Ren college of Biomass Science and Engineering Healthy Food Evaluation Research CenterSichuan UniversityChengdu 610065China Department of Chemistry College of ScienceKing Saud UniversityRiyadh 11451Saudi Arabia School of Life Sciences Pharmacy and ChemistryKingston University LondonKingston Upon Thames KT12EEUK

Mercury is a threatening pollutant in food,herein,we developed a Tb^(3+)-nucleic acid probe-based label-free assay for mix-and-read,rapid detection of mercury *** assay utilized the feature of light-up fluorescence of terbium ions(Tb^(3+))via binding with single-strand *** ion,Hg^(2+)induced thymine(T)-rich DNA strand to form a double-strand structure(T-Hg^(2+)-T),thus leading to fluorescence *** on the principle,Hg^(2+)can be quantified based on the fluorescence of Tb^(3+),the limit of detection was 0.0689μmol/L and the linear range was 0.1-6.0μmol/*** to the specificity of T-Hg^(2+)-T artificial base pair,the assay could distinguish Hg^(2+)from other metal *** recovery rate was ranged in 98.71%-101.34%for detecting mercury pollution in three food *** assay is low-cost,separation-free and mix-to-read,thus was a competitive tool for detection of mercury pollution to ensure food safety.

关键词： Mercury pollution Food safety Nucleic acid probe Label-free Terbium

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